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Hints of an Early Antibody Arsenal

Researchers think they've pinpointed the genetic precursors of the vertebrate immune system in the tiny sea creature, amphioxus. If they're right, amphioxus might provide a glimpse of the genes that laid the foundation for our immune system, 550 million years ago.

Although all animals have ways of protecting themselves against pathogens, only jawed vertebrates possess a full-blown "adaptive" immune system, able to fend off diverse attackers and provide immunity against repeat attacks. The immune system does this by creating a vast array of antibodies from combinations of immunoglobulin proteins encoded by a relatively small number of genes. But this shuffling act makes it hard to identify and compare immunoglobulin genes of different organisms, thwarting attempts to trace the evolution of the adaptive system.

Now, immunologists John Cannon, Robert Haire, and Gary Litman of the H. Lee Moffitt Cancer Center and Research Institute and the University of South Florida, St. Petersburg, have made progress with a novel gene cloning method. The team searched the genome of amphioxus, a "protochordate" whose lineage branched off just before vertebrates arose and 100 million years earlier than sharks, for genes encoding immunoglobulins.

The team identified five families of immunoglobulin genes like those that give the vertebrate system its great flexibility. Based on the DNA sequence of these genes, the team predicts that the resulting immunoglobulins would have diverse shapes in an important region called the V domain. The striking diversity, even within individuals of the species, suggests that these genes may represent an early step toward an adaptive immune system. Although amphioxus doesn't have a truly adaptive immune system, the newly identified genes seem to play a role in protecting the animal against pathogens it ingests while filter-feeding: Many of the amphioxus immunoglobulins can bind to chitin, a compound commonly found in microbes. The study is published online today in Nature Immunology.

The team's discovery is "an important contribution to the field of evolution and immunity," says evolutionary immunologist Diana Laird of Stanford University. But Werner Mueller of Gutenberg University in Mainz, Germany, protests that sponges--which evolved far earlier than amphioxus--are the true innovators, because his group has found V domains in them too. But Litman counters that those domains are not as diverse as the ones in amphioxus.